In new study, we show that SARS-CoV-2 has evolved decreased inherent antigenicity in humans, as quantified by a ~3-fold decrease in the number of naïve human B cells that can bind the spike RBD. doi.org
doi.org
It’s known SARS-CoV-2 evolves to erode antibodies from prior infection/vaccination. We asked: has it also become inherently less recognized by human germline antibodies? As shown below, answer is yes. ~3-fold fewer naïve human B cells bind newer vs old viral variant RBDs.
Importantly, this decrease in inherent antigenicity is specific to the human antibody repertoire. Mice naïve B cells bind newer vs older viral variant RBDs similarly (see below).
Our interpretation: early viral variant RBDs strongly targeted by “public” human germline antibodies, putting pressure on virus to change those epitopes. As epitopes mutated, sometimes they became less recognized by human germline repertoire, decreasing inherent antigenicity. However, decrease in inherent antigenicity is modest (~3-fold), and plenty of naïve human B cells still bind newer variant RBDs. We lack data to assess how much ~3-fold drop in inherent antigenicity affects human neutralizing antibody response. Interesting area for future work. This study was led by Catherine Jacob-Dolan in collaboration with @jimboonya.bsky.social Given some follow-up posts re this study (especially on X), I am pasting as image below last paragraph of Discussion. Multiple studies (eg, pmc.ncbi.nlm.nih.gov, thelancet.com show exposure to new variants still elicits antibodies, albeit w different specificities.
So while I'm unaware of head-to-head quantitative assessments of human post-primary exposure homologous titers to newer vs older variants, but primary exposure to new variants still elicits decent homologous neutralizing antibody titers. More generally, reduced inherent antigenicity to naive B cells is one mechanism (alongside glycan masking & positioning of RBD in down conformation) by which evolution of human endemic CoV can affect antibody elicitation. Understanding these mechanisms can improve vaccine / antibody development. However, newer viral variants remain immunogenic, albeit probably at modestly reduced levels--so this work does not support alarmism about immunity no longer recognizing SARSCoV2. Antibody response has amazing ability to recognize diverse antigens, although it recognizes some more easily than others